title: Effect of prenatal hypoxia in transgenic mouse models of preeclampsia and fetal growth restriction.
abstract: Mice lacking endothelial nitric oxide synthase (eNOS(-)(/-)) or catechol-O-methyl transferase (COMT(-/-)) exhibit a preeclampsia-like phenotype and fetal growth restriction. We hypothesized that a hypoxic insult would result in a more severe phenotype. Pregnant eNOS(-/-), COMT(-/-) and control (C57BL/6J) mice were randomized to hypoxic (10.5% O(2)) or normal conditions (20.9% O(2)) from gestational day 10.5 to 18.5. Hypoxia increased the blood pressure in all genotypes and proteinuria in C57BL/6J and eNOS(-/-) mice. Fetal survival was significantly reduced following hypoxia, particularly in eNOS(-/-) mice. Birth weight was decreased in both C57BL/6J and COMT(-/-) mice. Placentas from COMT(-/-) mice demonstrated increased peroxynitrite. Despite similar hypoxia-induced effects on maternal blood pressure and proteinuria, eNOS(-/-) embryos have a decreased tolerance to hypoxia. Compared to C57BL/6J, COMT(-/-) mice exhibited less severe changes in proteinuria and fetal growth when exposed to prenatal hypoxia. This relative resistance to prenatal hypoxia was associated with a significant increase in placental levels of peroxynitrite.
authors.affiliation: 1Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: C F
authors.initials: CF
authors.lastname: Rueda-Clausen
authors.forename: J L
authors.initials: JL
authors.lastname: Stanley
authors.forename: D F
authors.initials: DF
authors.lastname: Thambiraj
authors.forename: R
authors.initials: R
authors.lastname: Poudel
authors.forename: S T
authors.initials: ST
authors.lastname: Davidge
authors.forename: P N
authors.initials: PN
authors.lastname: Baker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002394:Catechol O-Methyltransferase / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics; D018384:Oxidative Stress; D030421:Peroxynitrous Acid / Q000378:metabolism; D010641:Phenotype; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D011247:Pregnancy; D011507:Proteinuria / Q000209:etiology; D012039:Regional Blood Flow; D012307:Risk Factors; D012720:Severity of Illness Index; D055988:Uterine Artery / Q000503:physiopathology
chemical_list: D030421:Peroxynitrous Acid; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; C000593198:COMT protein, mouse; D002394:Catechol O-Methyltransferase
keywords: fetal growth restriction; hypoxia; preeclampsia